Induced schizophrenic like breathing pattern leads to impaired cardiorespiratory coupling in healthy subjects

Schizophrenia is referred to as one of the most severe mental disorders in the world, and patients with this condition are associated with high cardiac mortality rates. However, the reasons for this high mortality rates are still under debate. One major contributing factor seems to be that a dysfunction of the autonomic nervous system (ANS) is evident in schizophrenia. Thereby, recent investigations focused on the analyses of respiration and cardiorespiratory coupling (CRC) in these patients.The objective of this study was to characterize the causal strength and direction of CRC applying the normalized short time partial directed coherence (NSTPDC) approach in healthy subjects (CON). In this study 25 healthy control subjects were enrolled matching in terms of age and gender to schizophrenic patients. CON were measured in resting condition (pre), breathing with schizophrenic like breathing pattern (stress) and resting condition for recovery (post). During stress CON were asked to breathe with a controlled fixed respiratory frequency, inspirationand expiration time. We found during induced stress significantly increased heart rate and reduced heart rate variability, increased breathing rate and reduced respiratory variability as well as impaired CRC for CON. In conclusion, during induced pathological breathing pattern CON exhibit an impaired and altered heart rate and respiratory regulation and CRC as indicators of a vagal withdrawal and sympathetic overdrive by the ANS. CRC analyses revealed impaired coupling strength and direction, with a driver-responder relationship from respiration to heart rate during stress. These findings support the central role of the respiratory dysregulation in schizophrenia and the assumed suppression of higher regulatory centers of the brain stem due to arousals and permanent stress situations in acute schizophrenia.